Abstract Focused ultrasound (FUS) is an early-stage, noninvasive therapeutic technology with great potential in oncology. FUS could potentially offer either an alternative or complementary strategy to existing cancer treatment approaches such as surgery, radiation, and immunotherapy. While FUS technology has some initial traction, there are still many unknowns about how best to deliver FUS and mechanisms of action. The work proposed herein will result in a platform that will accelerate the translational pace of this promising treatment modality. SonoVol is proposing to build and validate a novel FUS guidance, treatment, and assessment platform for small animals. The system will be deployed in SonoVol?s Vega, a robotically controlled volumetric scanning device for high-throughput preclinical imaging. Unlike conventional FUS research solutions, the new 3D image guided ?TherUS? Platform will ensure accurate and repeatable FUS dose delivery irrespective of user or sonographer expertise. TherUS will accelerate FUS clinical translation by lowering the technological barriers which limit widespread access, putting the technology directly in the hands of the broader market of cancer biologists and immunologists to develop cutting-edge anticancer treatment strategies, including immunotherapy approaches. This work will proceed via three stages. First, we will develop hardware to allow accurate and repeatable dose delivery via multiple FUS transducers within the same study. Two transducers with center frequencies of 0.5 and 2 MHz will be installed in a robotic carriage and the pressure fields will be mapped to allow spatial localization with the guidance and follow up transducers. Second, we will develop software to facilitate treatment planning and confirmation of dose delivery. We will create a module to allow registration to previous timepoints, as well as dose confirmation algorithms within SonoVol?s software for thermometry and cavitation detection. Finally, we will compare accuracy, repeatability, and reproducibility of TherUS against a conventional top-down FUS system and prove in vivo feasibility with an ablation study in a mouse model of breast cancer.